The purpose of these studies is to establish the basic developmental and cellular events operating in regulating the genes for fetal (gamma) and adult (betaA and betaC) globin sheep erythroid cells. Induction of Hb C may be achieved in vitro or in vivo by exposure of erythroid stem cells to high erythropoietin (epo) concentration. The amount of Hb C synthesis appears to be related to the degree of differentiation of stem cells which give rise to erythroid colonies in vitro; the earliest stem cells give rise to colonies making more Hb C. The perinatal switch from Hb F (Alpha2gamma2) to Hb A (Alpha2BetaA2) also appear to be regulated in hematopoietic stem cells although the progenitors which can be assayed in vitro appear to have already been committed with respect to the hemoglobin produced in the erythroblasts which are their progeny. We have developed a transplantation model to investigate whether such committment is instrinsic to the stem cells or related to the micro-environment of these cells. Successful engrafment of stem cells from an animal at the immediate pre-switch stage into a mild-gestation fetus has been documented in one fetus although no adult hemoglobin production was found.